Let’s start with some biochemistry.

Piruvate, the product of glycolysis, can enter in Krebs cicle to produce energy through aerobic (oxygen driven) process or can take a shorter and faster (x100 times) way to produce energy when is transformed to lactate (the basis of lactic acid) using NADH (so reduced to NAD+ and ready to take another H+) and H+.

No hydrogen ions are present in glycolysis. In fact, the conversion of pyruvate to lactate consumes hydrogen ions. It is actually a lactic alkalosis. (J Mol Cell Cardiol 1997;9[11]:867.)

Increased lactate may simply occur because of increased production of pyruvate due to in- creased glycolysis there is no oxygen debt. We spoke about the muscles exporting lactate; the same thing happens in shock: lactate is used as a fuel for oxidative metabolism. Lactate is transported into the mitochondrion through specific transport proteins, and then is converted to pyruvate in the mitochondrial intermembrane space. Pyruvate then moves into the mitochondrial matrix and undergoes oxidative metabolism.Lactate is, therefore, a fuel for oxidative metabolism. It’s consumed by the brain and heart, and that is absolutely vital to survival when someone is in shock.

So why is lactate produced and used for?

Lactate is aerobically producted by muscle and is a more efficient source of energy for the brain and the heart.

Lactate is a much more efficient bioenergetic fuel than glucose so as someone exercises, the muscles make lactate to fuel the heart. The heart works much more efficiently with lactate. What happens to the brain? The exact same thing. As someone exercises, brain lactate goes up, and the brain starts using lactate preferentially as a source of fuel. This is a brilliant design: Muscles make lactate aerobically as a source of energy for the brain and heart.

Lactic metabolic acidosis is a biochemical myth! It’s more a lactic alkalosis.

The lactic acidosis explanation of metabolic acidosis is not supported by fundamental biochemistry, and has no research basis. Acidosis is caused by reactions other than lactate production.

No hydrogen ions are present in glycolysis. In fact, the conversion of pyruvate to lactate consumes hydrogen ions. It is actually a lactic alkalosis. (J Mol Cell Cardiol 1997;9[11]:867.)

Hypoxia does not induce lactate serum level elevation, and in sepsis oxygen cellular level is not decreased.

There is this pervasive idea that people with sepsis have cellular hypoxia and bioenergetic failure, but this concept was debunked in 1992. Compared with limited infection, the muscle O2 goes up in patients with severe sepsis.

Increased lactate may simply occur because of increased production of pyruvate due to increased glycolysis there is no oxygen debt. We spoke about the muscles exporting lactate; the same thing happens in shock: lactate is used as a fuel for oxidative metabolism. Lactate is, therefore, a fuel for oxidative metabolism. It’s consumed by the brain and heart, and that is absolutely vital to survival when someone is in shock. The body makes lactate, which is then used as a metabolic fuel.

Iperlactic state is generated, by epinephrine and not by hypoxia, in case of extreme physiological stress as protective mechanism.

The clinical plausibility was that lactate increases during adrenergic states and in the absence of an oxygen debt. Lactate increases with epinephrine infusion; lactate increases with hyperdynamic sepsis. All of the states have a high cardiac output, high oxygen delivery, and not a single trace of hypoxia. It’s driven by epinephrine, not by hypoxia.

We do know that lactate is associated with increased mortality because the sicker a patient is, the higher his epinephrine levels. It’s a protective mechanism. The association is related to the fact that lactate is a biomarker of physiological stress. And clearly the greater the physiological stress, the greater the risk of death. But lactate itself is a survival advantage, and it’s not an evolutionary accident that we make lactate.

Credits:

Thanks to the author and to Aidan Baron who originally shared the article.

2 Risposte to ““Humans Are Not Yeast”: (almost) everything we believe about lactate is a myth. ”

1. Acidosis could be described in terms of “strong ion difference” (SID). Lactate is a strong anion that will decrease SID and will lower the pH (Stewart approach). So there IS acidosis whatever the fate of H+.

2. As I recall, in severe sepsis there is uncoupling of oxydative phosporilation so that’s why the tissue O2 actually builds up (=it is not consumed=the final step in respiration). In fact, a low SaO2-SvO2 difference is a poor sign in septic shock. Lactate will accumulate exactly like in true hypoxia.

3. Local acidemia and hypercarbia will enhance hemoglobin unloading and tissue oxygenation.